This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Potassium channels facilitate the rapid selective diffusion of K+ ions across the cell membrane through their ion conduction pore. Many diverse molecules can plug the pore and modulate the K+ current, which often serves as an important regulatory function in certain families of K+ channels, such as inward rectifier K+ (Kir) channels and some voltage-gated K+ channels. Channel blocking molecules are of great pharmacological interest, because many commonly prescribed drugs unintentionally cause blockage as a negative side-effect. Such side-effects can be life-threatening in certain cases. Furthermore, some channel blockers have served as experimental probes that have greatly expanded our understanding of K+ channel function. A detailed structural interpretation of channel blockage mechanisms may ultimately lead to significant improvements in treatments for human diseases.